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Diabetes in the paediatric population

By Dr Kevin Conlon - 16th Apr 2023

chronic diseases

Diabetes is one of the most common chronic diseases in the world, with an estimated one-in-11/12 people worldwide affected by it (more in some countries).1 The vast majority of cases are found in adults, but it remains a significant health burden for children worldwide, behind only asthma in prevalence among chronic diseases of childhood. It is important therefore that any medical professional working with children is comfortable with the diagnosis of diabetes, its day-to-day management, and the recognition and treatment of diabetic emergencies.

Traditionally, diabetes was defined as either insulin-dependent or non insulin-dependent, but the current approach sees diabetes defined by its mechanism of action.2

Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterised by destruction of beta cells of the pancreas, leading to an absolute insulin deficiency.3 It occurs in individuals with a genetic susceptibility, typically following a trigger by an environmental agent such as a virus, and as the initial progression of beta cell destruction takes place the patient initially remains asymptomatic. T1DM currently accounts for greater than 95 per cent of cases of diabetes mellitus in paediatric populations in the UK and Ireland. Type 2 diabetes mellitus (T2DM) is most typically seen as a disorder of insulin resistance associated with a relative insulin deficiency.4 While more common in adult populations, T2DM was traditionally uncommon in paediatric populations. However, with the growing problem of childhood obesity (particularly in the Western world), T2DM is becoming a more common paediatric diagnosis in late adolescence.

Secondary forms of diabetes mellitus also exist; cystic fibrosis-related diabetes (CFRD) is a complication of CF associated with a relative rather than absolute insulin deficiency following beta cell destruction, but with some elements of insulin resistance also noted.5 It has been associated with increased morbidity and mortality in this patient cohort. Mature onset diabetes of the young (MODY) is an autosomal-dominant condition associated with ineffective insulin production or secretion and is caused by a single gene defect in one of a number of recognised genes.6 For this reason, it is also known as monogenic diabetes. There are other, rarer causes of diabetes mellitus in the paediatric population, including gestational diabetes in the case of pregnancy.

Presentation

The typical presentation of diabetes mellitus is with a classic triad of symptoms (polydipsia, polyuria, and weight loss) and a raised blood glucose of >11.1mmol/L. Other symptoms that can also be features of presentation include nocturnal enuresis, lethargy, blurred vision, increased appetite, recurrent infections, slow-healing injuries, and constipation.7

Patients should have their blood glucose, blood ketones, and blood gases assessed at time of first presentation, and it is recommended to have blood tests sent to look for the presence of autoantibodies associated with T1DM (anti-GAD, anti-IA2 and anti-ZnT8 antibodies).

Diabetic ketoacidosis

It is also possible for patients to present in diabetic ketoacidosis (DKA) as a first presentation of diabetes mellitus; a recent study of an Irish paediatric population shows that 25 per cent of presentations with T1DM were in DKA, with a higher level in children aged under two years.7

DKA is a medical emergency and is the leading cause of morbidity and mortality among the paediatric T1DM population,8 with the rare case of mortality occurring as a result of cerebral oedema.9 In DKA, high levels of glucose unchecked by insulin cause osmotic diuresis in the kidneys, leading to polyuria and dehydration; as well as causing beta oxidation of free fatty acids into ketones, which cause metabolic acidosis.10

The aims of managing DKA are to correct acidosis, reverse ketosis, correct dehydration, restore blood glucose to near-normal, monitor for complications of DKA, and treat any underlying cause for DKA.9 Initial management is with assessment and resuscitation as required, including the use of boluses of 0.9 per cent NaCl to restore circulating volume. Following this initial stage, fluid requirements should be calculated to account for both maintenance requirements and the fluid deficit present in the patient and this should be administered over 48 hours. DKA is a naturally hypokalaemic state, with depletion of total body potassium through osmotic diuresis; however, initial serum potassium levels can appear normal. KCI should be added to IV fluids once urine output is confirmed or blood tests confirm the patient is not hyperkalaemic.

Insulin administration should be delayed until at least one hour after maintenance fluids have begun; this is associated with a lower risk of cerebral oedema.9 Despite being associated with acidosis, there is no role for bicarbonate in the management of DKA, and evidence suggests it is associated with a greater risk of worsening tissue hypoxia and cerebral acidosis.

Management

The long-term treatment and management of each variant of diabetes mellitus should be appropriate for the underlying pathophysiology behind each individual subtype. As T1DM is fundamentally caused by a lack of insulin, the treatment required for patients with T1DM is insulin.11 The decision regarding what particular insulin regime to commence in a well patient should be made following consultation with a consultant paediatric endocrinologist, but in general starting doses vary between 0.75-1.0 units/kg/day. 

This total daily dose of insulin can then be divided between long-acting basal insulin (eg, Levemir, Lantus, Tresiba) and short-acting bolus insulin (eg, NovoRapid, Fiasp).

A typical starting ratio is to divide the total daily insulin dose into 50 per cent basal and 50 per cent bolus insulin;12 basal insulin is designed to replace background endogenous insulin and is given once or twice a day, while bolus insulin is given prior to eating and is typically divided in three doses (pre-breakfast, pre-lunch, and pre-dinner). These initial set doses for bolus insulin will ideally give way in time to more precise doses calculated, based on the amount of carbohydrate in the meal about to be eaten, following education.

Initial management for a new diagnosis of T1DM should focus on commencing insulin as outlined above, as well as education for the family around the essential skills required for living with diabetes.13 This includes information about what diabetes is, a basic management routine, developing the skills of blood glucose testing and insulin administration, and management of hypoglycaemia, hyperglycaemia, and intercurrent illness. Future education sessions should focus on strategies for optimising good glycaemic control.

Outpatient appointments should be offered every three months for clinical examination and assessment of glycaemic control through review of blood glucose diaries/blood glucose sensor data and monitoring of HbA1c.14 Annual review appointments should include screening for common autoimmune conditions (thyroid disease, Coeliac disease), screening for microalbuminuria, and a lipid profile. After the age of 12, referral should be made to the Diabetic Retinopathy Screening Programme (www.diabeticretinascreen.ie).

For both T1DM and T2DM, the role of the multidisciplinary team (MDT) is a central feature of patient management. Patients should have access to endocrinologists, diabetes clinical nurse specialists, dieticians, and psychologists. The most important initial function of the MDT is structured education for both day-to-day management and management of diabetes-related emergencies.11

Insulin pumps and CGM

Continuous subcutaneous insulin infusion (CSII) therapy, also known as ‘insulin pumps’, is rapidly becoming the standard of care for paediatric patients in health systems in the developed world.15 They work by continuously delivering a basal rate of rapid-acting insulin via a subcutaneous giving set, replacing the need for long-acting insulin – this delivery of insulin more closely resembles the physiological action of insulin in the body of a person without diabetes.

This move towards CSII therapy is occurring alongside developments in blood glucose monitoring.

Continuous glucose monitoring (CGM) uses a subcutaneous sensor to measure interstitial glucose levels and offer real-time feedback on blood glucose levels; it is considered to be the preferred option of blood glucose monitoring in the paediatric setting.16 CGM also offers a new therapeutic goal by providing information on how long a patient spends within a normal range for blood glucose; this ‘time in range’ value is considered more accurate than HbA1c as it is not confounded by episodes of hypoglycaemia.17

There is a new generation of CSII pumps which have the ability to communicate with CGM sensors to offer a number of functions, including suspending insulin delivery if blood glucose falls below a certain value, or real-time alteration of insulin delivery in response to blood glucose levels (the hybrid closed-loop system). As CSII and CGM technology improves, it continues to offer patients with T1DM more opportunities to maintain good glycaemic control, reduce the risk of adverse effects, and improve quality-of-life.

T2DM management

The management of T1DM contrasts with T2DM, which rather than being a failure of insulin production is instead caused by a problem with the action of insulin in the body. As such, the mainstay of treatment is not insulin therapy, with first-line advice being management of diet and exercise to counter the risk of insulin resistance.14 Aside from these non-pharmacological interventions, there are several medications which have a role in T2DM management; metformin decreases glucose production in the liver and increases sensitivity to insulin in the body tissues;14 GLP1 agonists (eg, liraglutide, semaglutide) enhance glucose-mediated insulin secretion and reduce postprandial glucagon secretion;18 and insulin may be required by a small proportion of T2DM patients, but is recommended for any T2DM patient with evidence of ketosis or who have a significant raised blood glucose level (HbA1c >69mmol/mol).19

Future

The future of T1DM management is moving away from novel therapies and focusing on screening and immunotherapies for prevention. Recent studies taking place around the world are investigating the role of autoantibodies as predictors of T1DM, both in families with a history of T1DM and in general populations.20,21 Although at the early stages of development, the possibility of someday being able to prevent T1DM is an exciting one, and mirrors the innovation which has already transformed the management of diabetes since Banting and Best first isolated insulin just over 101 years ago. For patients and staff alike, the next century looks to be just as exciting as the last.

National clinical guidelines on diabetes in children

A Model of Care for all children and young people with type 1 diabetes was published in 2015. The primary aim of this model of care is to define excellent diabetes care, and improve access, quality, and value for all children with T1DM in Ireland. That document is available at: www.hse.ie/eng/about/Who/clinical/natclinprog/paediatricsandneonatology/paedsmoc.pdf.

A Model of Care was developed in 2012 for the provision of continuous subcutaneous insulin infusion (CSII) therapy in children aged under five years of age and was updated in March 2015. That document is available at: www.lenus.ie/hse/bitstream/10147/275652/1/ProvisionContinSubcutaInsuInfusiontreat Type1DiabetesUnderFives.pdf.

In March 2019 the HSE published a series of national clinical guidelines on diabetes care in children, with a number of updates and additions since then: Care of the child newly diagnosed with type 1 diabetes without DKA (updated April 2021); Identification and management of hypoglycaemia in children with type 1 diabetes (updated April 2021); Annual review and co-morbidity screening in type 1 paediatric diabetes (Version 1, November 2020); Management of continuous glucose monitoring for children type 1 diabetes (Version 1, October 2020); Management of paediatric type 1 diabetes patient with a HbA1c >9 per cent (75mmol/mol) (Version 3, March 2019); General principles in the management of children with diabetes requiring surgery (updated April 2021); Management of paediatric diabetic ketoacidosis (updated April 2021); Management of paediatric type 1 diabetes patient with an intercurrent illness (hospital) (updated April 2021); and Management of paediatric type 1 diabetes patient who did not attend (DNA), were not brought or repeatedly cancels their appointments (March 2019).

All these clinical guidelines can be accessed at: www.hse.ie/eng/about/who/cspd/ncps/paediatrics-neonatology/resources/.

For parents and caregivers, there is also a Paediatric Type 1 Diabetes Resource Pack, which was developed jointly by paediatric clinical nurse specialists and dietitians working in Irish specialist services on behalf of the National Clinical Programme for Paediatric Diabetes. The aim is to give a clear, concise advice on common scenarios as the parent/child begins learning about diabetes. It is available at: www.hse.ie/eng/about/who/cspd/ncps/paediatrics-neonatology/resources/paediatric-type-1-diabetes-resource-pack.pdf.

The latest HSE document is the Meeting the care needs of primary school children with type 1 diabetes during school hours guideline, which is a useful resource for parents, carers, teachers, and school staff and was published in the summer of 2022. The document sets out clear guidelines that will help structure the conversation and preparations between the family, diabetes team, and school staff. It explains diabetes and diabetes management to teachers and school staff and sets out clear lines of responsibility for all partners. The document also includes a Personal Pupil Plan to agree on current diabetes management and the needs of a child, which includes information, such as personal hypoglycaemia symptoms, what to eat during hypoglycaemia, and when to check glucose levels and deliver insulin. The school can have a personalised ‘information pack’ for all their pupils with T1DM. This document can be accessed at: www.hse.ie/eng/about/who/cspd/ncps/paediatrics-neonatology/resources/meeting-care-needs-primary-school-children-with-diabetes1.pdf.

References

1. International Diabetes Federation. IDF Diabetes Atlas. 2021. Available at: https://diabetesatlas.org/

2. World Health Organisation. Diabetes factsheet. 2022. Available at: www.who.int/news-room/fact-sheets/detail/diabetes

3. Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med. 1994 Nov 24;331(21):1428-36

4. Temneanu OR, Trandafir LM, Purcarea MR. Type 2 diabetes mellitus in children and adolescents: A relatively new clinical problem within paediatric practice. J Med Life. 2016 Jul-Sept;9(3):235

5. Moran A, Doherty L, Wang X, Thomas W. Abnormal glucose metabolism in cystic fibrosis. J Paediatr. 1998 Jul 1;133(1):10-7

6. Sanyoura M, Philipson LH, Naylor R. Monogenic diabetes in children and adolescents: Recognition and treatment options. Curr Diab Rep. 2018 Aug;18(8):1-3

7. Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes. Paediatric Diabetes. 2005 Jun;6(2):75-8

8. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child. 1999 Oct 1;81(4):318-23

9. HSE. Management of paediatric diabetic ketoacidosis. 2021. Available at: www.hse.ie/eng/about/who/cspd/ncps/paediatrics-neonatology/resources/management-of-paediatric-diabetic-ketoacidosis1.pdf

10. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycaemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul 1;32(7):1335-43

11. HSE. Care of the child newly diagnosed with type 1 diabetes without DKA. 2021. Available at: www.hse.ie/eng/about/who/cspd/ncps/paediatrics-neonatology/resources/care-of-the-child-newly-diagnosed-with-type-1-diabetes-without-dka.pdf

12. Levitsky LL, Misra M. Insulin therapy for children and adolescents with type 1 diabetes mellitus. 2022. Available at: www.uptodate.com/contents/insulin-therapy-for-children-and-adolescents-with-type-1-diabetes-mellitus

13. Haller MJ, Atkinson MA, Schatz D. Type 1 diabetes mellitus: Etiology, presentation, and management. Paediatric Clinics. 2005 Dec 1;52(6):1553-78

14. American Diabetes Association. 13. Children and adolescents: Standards of medical care in diabetes – 2021. Diabetes Care. 2021 Jan 1;44(Supplement_1):S180-99

15. Phillip M, Battelino T, Rodriguez H, Danne T, Kaufman F. Consensus Forum Participants. Use of insulin pump therapy in the paediatric age-group: Consensus statement from the European Society for Paediatric Endocrinology, the Lawson Wilkins Paediatric Endocrine Society, and the International Society for Paediatric and Adolescent Diabetes, endorsed by the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2007 Jun 1;30(6):1653-62

16. Chiang JL, Kirkman MS, Laffel LM, Peters AL. Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: A position statement of the American Diabetes Association. Diabetes Care. 2014 Jul 1;37(7):2034-54

17. American Diabetes Association. Diabetes technology: Standards of medical care in diabetes – 2020. Diabetes Care. 2020 Jan 1;43(Supplement 1):S77-88

18. Lee YS, Jun HS. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism. 2014 Jan;63(1): 9-19

19. Copeland KC, Silverstein J, Moore KR, Prazar GE, Raymer T, Shiffman RN, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Paediatrics. 2013 Feb;131(2):364-82

20. Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, et al. The TrialNet Natural History Study of the development of type 1 diabetes: Objectives, design, and initial results. Paediatric Diabetes. 2009 Mar;10(2):97-104

21. McCulloch DK, Palmer JP. The appropriate use of B-cell function testing in the preclinical period of type 1 diabetes. Diabetic Medicine. 1991 Nov;8(9):800-4

Dr Kevin Conlon, Paediatric Endocrinology SpR, Children’s Health Ireland (CHI) at Crumlin. Reviewed by Prof Declan Cody, Consultant in Paediatric Endocrinology and Diabetes, CHI Crumlin, and Clinical Professor, University College Dublin

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